title: Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial.
abstract: OBJECTIVE
  To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial.
  
  
  METHODS
  The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects.
  
  
  RESULTS
  Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose-volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034).
  
  
  CONCLUSIONS
  Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.
authors.affiliation: Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri. Electronic address: jmichalski@radonc.wustl.edu.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Michalski
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Deborah
authors.initials: D
authors.lastname: Watkins-Bruner
authors.forename: Walter R
authors.initials: WR
authors.lastname: Bosch
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
authors.forename: James M
authors.initials: JM
authors.lastname: Galvin
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Morton
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Parliament
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D006801:Humans; D016015:Logistic Models; D008297:Male; D058958:Organs at Risk / Q000528:radiation effects*; D011467:Prostate / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011785:Quality Assurance, Health Care; D044469:Racial Groups; D011832:Radiation Injuries / Q000150:complications* / Q000473:pathology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012007:Rectum / Q000528:radiation effects; D012669:Seminal Vesicles / Q000528:radiation effects; D047368:Tumor Burden; D001743:Urinary Bladder / Q000528:radiation effects